Sources Sought_75N95023R00004.pdf

Notice ID: 75N95023R00004 Sources Sought

Pharmacology Studies and Animal Model Development and Related Services for Drug Development

Classification Code/Title: AN12 - Health R&D Services; Health care services; Applied Research

NAICS Code/Title: 541714 - Research and Development in Biotechnology (except Nanobiotechnology)

Related Notice: Request for Information, Notice ID 75N95023R00004, Pharmacology Studies and Animal Model Development and Related Services for Drug Development, published November 7, 2022.

PURPOSE OF NOTICE

This is a Research and Development (R&D) Sources Sought notice. This is NOT a solicitation for proposals, proposal abstracts, or quotations. The purpose of this notice is to obtain information regarding the availability and capability of all qualified sources to perform a potential R&D requirement.

This notice is issued to help determine the availability of qualified companies technically capable of meeting the Government requirement and to determine the method of acquisition. It is not to be construed as a commitment by the Government to issue a solicitation or ultimately award a contract.

Responses will not be considered as proposals or quotes. No award will be made as a result of this notice. Responses will not be considered as proposals or quotes. The Government will NOT be responsible for any costs incurred by the respondents to this notice. This notice is strictly for research and information purposes only. The Government will not entertain questions regarding the results of this market research.

BACKGROUND

The Therapeutic Development Branch (TDB) within the Division of Preclinical Innovation (DPI) at the National Center for Advancing Translational Sciences (NCATS) within the National Institutes of Health (NIH) conducts translational research to support therapeutic development by moving small molecule and biologic drug candidates forward in the drug development pipeline. Upon reaching predetermined milestones, TDB hands off clinical candidates to external partners to bring these novel therapies to patients. In addition to developing new candidate drugs, TDB seeks to advance the entire field of drug discovery and development by encouraging scientific and technological innovations aimed at improving success rates in the crucial preclinical stage of drug development. The TDB model is to operate as a comprehensive small molecule and biologics drug development organization, moving therapeutic candidates through each phase of the preclinical development process until an Investigational New Drug (IND) application is filed with the US Food and Drug Administration (FDA). For certain drug development campaigns, TDB will support studies up to human Phase IIb. TDB conducts drug development through collaborations, with therapeutic candidates originating from academia, industry, non-profit foundations, or internally from NCATS and other NIH institutes. TDB’s operational strategy is to combine the capabilities of in-house staff and collaborative partners with complementary support from contract research organizations (CROs). Each development program operates in a multi-disciplinary matrix team environment, with NCATS responsible for overall planning and execution.

The NCATS has an existing single-award IDIQ contract for CRO Support for NCATS Efficacy and In Vivo Pharmacology Studies and Related Services. This potential procurement would be a re-competition of this existing contract with some technical and administrative updates. The incumbent is Lovelace Biomedical Research Institute, Contract No. 75N95019D00012.

PURPOSE AND OBJECTIVES

The purpose of this Sources Sought is to obtain information about vendor capabilities to support Pharmacology Studies and Animal Model Development and Related Services for Drug Development.

The objectives of this potential acquisition are to obtain information about the biological effects of test articles on cellular and organismal function during the drug discovery and development process; to provide expertise in designing, executing, interpreting, and reporting on such studies, including in support of regulatory filings; and to optimize or develop relevant in vivo animal models and/or in vitro / ex vivo animal model replacement systems that support preclinical drug development efforts. The test article/product formats may include small molecules, short oligomeric compounds, biological (large) molecules, quaternary molecular assemblies (homogenous or heterogenous), vectors for gene therapy, nanoparticles, and any of the above modified genetically, biologically, or chemically. Novel formats identified after this draft might also be needed. Formats could also include Devices or Combination Products.

ANTICIPATED PERIOD OF PERFORMANCE

The potential IDIQ contract(s) are expected to have a seven-year ordering period. Task orders issued under the IDIQ contract(s) will have their own periods of performance that are based on the specific requirement.

PROJECT REQUIREMENTS

The potential acquisition is anticipated to be a multiple-award Indefinite Delivery / Indefinite Quantity (IDIQ) contract. The anticipated IDIQ contract(s) would include one or more of three separate technical areas:

Technical Area 1: In Vivo Pharmacology Services and Model Development in Small Animals

Technical Area 2: In Vivo Pharmacology Services and Model Development in Large Animals

Technical Area 3: In Vitro Pharmacology Studies in Ex Vivo Tissue-, Cell-Based, or Other Relevant Animal Replacement Models

The Government recognizes that contractors may be supported to a certain extent by consultants and/or subcontractors but contractors shall be responsible for all work performed to include project planning, initiation, implementation, management and communication; evaluation, selection, and management of subcontractors; and for all deliverables specified in this contract and each awarded Task Order.

Technical Area 1: In Vivo Pharmacology Services and Model Development in Small Animals

The Contractor shall provide services related to the conduct of in vivo studies with therapeutics under development. The studies under this technical area will be conducted using small animal models to support demonstration / verification of efficacy and further drug development activities. The Contractor also shall provide services related to the optimization / refinement of existing animal models or the development of novel models, including characterizing and validating such models to support drug development activities.

Anticipated in vivo pharmacology services under this technical area include, but are not limited to:

1. Defining pharmacokinetic / pharmacodynamic (PK/PD) relationships from existing data or by independently establishing the PK parameters for therapeutic candidates.

2. Optimizing / refining or developing biomarkers and efficacy endpoints.

3. Determining correct route of administration (e.g., SC, IV, PO, IT, or ICV).

4. Determining appropriate dosing parameters.

5. Determining appropriate formulation(s) for administration.

6. Evaluating efficacy and biomarkers in response to treatment with test article.

7. Examination of preliminary toxicity and safety parameters.

Anticipated model refinement / development services under this technical area may include, but are not limited to:

1. Developing novel or similarly existing genetically modified animals that are organ system-specific or whole-body targeted for stable or conditional knock-ins, knock-outs, knock-downs, overexpression, etc. using appropriate genomic techniques such as, but not limited to:

a. Generating targeting constructs per model requirement, including, plasmid DNA vector, single-stranded oligodeoxynucleotides (ssODNs), and ribonucleic acid interference (RNAi) (e.g., silencing ribonucleic acid (siRNA) or short hairpin RNA (shRNA)).

b. Use of cre-lox or tetracycline-induced technology.

c. Use of random DNA transgenesis or optimization of other delivery / gene editing system (e.g., CRISPR/Cas9 or recombinant adeno-associated viruses (rAAVs)-mediated or other applicable technology).

d. Transfection or electroporation of appropriate cells (e.g., skin fibroblasts (somatic) or embryonic stem (ES) cells) with targeting construct with appropriate gene/editing delivery system(s).

e. Conducting somatic cell nuclear transfer (SCNT) into oocytes, transgene pronuclear microinjection or ES cell microinjection into fertilized eggs for uterine implantation to generate required fetuses / harvest appropriate cells for downstream procedures as necessary including genetic characterization.

f. Cryopreservation of embryos or sperm or harvested fibroblast for SCNT to resuscitate model as needed for future studies.

2. Chemically- or diet-induced models (e.g., CNS, respiratory or metabolic).

3. Physiologically- or procedure-induced models (e.g., anemic).

4. Mechanically-induced models.

5. Single or multiple genetic crossings / breeding.

6. Re-derivation, back-crossing, etc. as necessary to optimize or refine existing models, if feasible and cost-effective.

7. Production of live animals of the model.

8. Basic phenotypic characterization / validation of the model and/or defining comprehensively the natural history of disease progression.

Technical Area 2: In Vivo Pharmacology Services and Model Development in Large Animals

The Contractor shall provide services related to the conduct of in vivo studies with therapeutics under development. The studies under this technical area will be conducted using large animal models, inclusive of non-human primates, to support demonstration / verification of efficacy and further drug development activities. The Contractor also shall provide services related to the optimization / refinement of existing animal models or the development of novel models, including characterizing and validating such models to support drug development activities.

Anticipated in vivo pharmacology services under this technical area include, but are not limited to:

1. Defining pharmacokinetic / pharmacodynamic (PK/PD) relationships from existing data or by independently establishing the PK parameters for therapeutic candidates.

2. Optimizing / refining or developing biomarkers and efficacy endpoints.

3. Determining correct route of administration (e.g., SC, IV, PO, IT, or ICV).

4. Determining appropriate dosing parameters.

5. Determining appropriate formulation(s) for administration.

6. Evaluating efficacy and biomarkers in response to treatment with test article.

7. Examination of preliminary toxicity and safety parameters.

Anticipated model refinement / development services under this technical area may include, but are not limited to:

1. Developing novel or similarly existing genetically modified animals that are organ system specific or whole-body targeted for stable or conditional knock-ins, knockouts, knock-downs, overexpression, etc. using appropriate genomic techniques such as, but not limited to:

a. Generating targeting constructs per model requirement (e.g., plasmid DNA vector, single-stranded oligodeoxynucleotides (ssODNs), and ribonucleic acid interference (RNAi) (e.g., silencing ribonucleic acid (siRNA) or short hairpin RNA (shRNA)).

b. Use of cre-lox or tetracycline-induced technology.

c. Use of random DNA transgenesis or optimization of other delivery / gene editing system (e.g., CRISPR/Cas9 or recombinant adeno-associated viruses (rAAVs)-mediated or other applicable technology).

d. Transfection or electroporation of appropriate cells (e.g., skin fibroblasts (somatic) or embryonic stem (ES) cells) with targeting construct with appropriate gene/editing delivery system(s).

e. Conducting somatic cell nuclear transfer (SCNT) into oocytes, transgene pronuclear microinjection or ES cell microinjection into fertilized eggs for uterine implantation to generate required fetuses / harvest appropriate cells for downstream procedures as necessary including genetic characterization.

f. Cryopreservation of embryos or sperm or harvested fibroblast for SCNT to resuscitate model as needed for future studies.

2. Chemically- or diet-induced models (e.g., CNS, respiratory or metabolic).

3. Physiologically- or procedure-induced models (e.g., anemic).

4. Mechanically-induced models.

5. Single or multiple genetic crossings / breeding.

6. Re-derivation, back-crossing etc. as necessary to optimize or refine existing models, if feasible and cost-effective.

7. Production of live animals of the model.

8. Basic phenotypic characterization / validation of the model and/or defining comprehensively the natural history of disease progression.

Technical Area 3: In Vitro Pharmacology Studies in Ex Vivo Tissue-, Cell-Based, or Other Relevant Animal Replacement Models

The Contractor shall conduct in vitro pharmacology studies to establish biomarkers and efficacy endpoints, and to test the efficacy and toxicity of therapeutics in existing, optimized / refined, or newly developed in vitro / ex vivo cell- or tissue-based models of disease or other relevant animal replacement models, including those derived from human samples.

The Contractor shall provide services related to the optimization / refinement of existing alternative animal replacement models or the development of such novel alternative animal replacement models. The Contractor shall characterize and validate such models to support drug development activities.

Anticipated in vitro / ex vivo models under this technical area include, but are not limited to:

1. Stably (immortalized) or transiently transfected genetically modified cell lines (e.g., knock-in, knock-down, knock-out, overexpressing transgene).

2. Unaffected or affected donor-derived cells (e.g., induced pluripotent stem cells (iPSCs) or progenitor or primary cells from human patients or animal models).

3. Tissue-chip technology (e.g., single or interconnected organ systems).

4. 3D cell- or tissue-based models (e.g., skin, liver, neuronal architecture).

5. Freshly harvested cells / tissues.

Anticipated in vitro / ex vivo study activities under this technical area include, but are not limited to:

1. Optimizing conditions / performing cell or tissue culture maintenance.

2. Optimizing / refining or developing biomarkers and efficacy endpoints.

3. Treatment with test articles, collection of samples (e.g., cells, tissues, fluids) and performance of relevant assays (e.g., protein concentration, imaging).

4. Performing relevant biomarker and/or efficacy assays.

5. Assessment of cell viability / toxicity.

INFORMATION REQUESTED

Vendors should provide a capability statement that addresses their capability and experience in one or more of the above technical areas. Vendors may provide a capability statement in one area, two areas, or all three areas. Vendors with prior, similar experience should clearly demonstrate that experience and include information on the size and scope of that experience. If prior experience was gained with the Government as a prime or subcontractor, describe the size and scope of the work and provide the contract number.

Capability statements should address each point listed under the applicable technical area(s). Capability statements must address the specific technical area(s) and points in this Notice; general capability statements will not be reviewed.

Vendors seeking to respond to this Notice as part of a teaming arrangement should include the requested information from each vendor in the proposed team.

RESPONSE INSTRUCTIONS

Responses must be submitted via email to Kimberly Espinosa at Kimberly.espinosa@nih.gov and should include the following:

a. Capability statement that addresses each point under one or more technical areas.

b. Cover Page that includes the following:

• Notice ID mailto:Kimberly.espinosa@nih.gov

• Unique Entity Identifier (UEI)

• Company Name

• Company Address

• Company Point of Contact, Phone, and Email address

DISCLAIMER AND IMPORTANT NOTES

This notice does not obligate the Government to award a contract or otherwise pay for the information provided in response. The Government reserves the right to use information provided by respondents for any purpose deemed necessary and legally appropriate. Any organization responding to this notice should ensure that its response is complete and sufficiently detailed to allow the Government to determine the organization’s qualifications to perform the work.

Respondents are advised that the Government is under no obligation to acknowledge receipt of the information received or provide feedback to respondents with respect to any information submitted.

After a review of the responses received, a pre-solicitation synopsis and solicitation may be published in SAM. However, responses to this notice will not be considered adequate responses to a solicitation.

To enable Collaborators to retain control of intellectual property created under the anticipated IDIQ contracts, the Government is seeking a Declaration of Exceptional Circumstances (DEC) to the Federal Acquisition Regulations (FAR) for this program, in which case HHSAR Clause 352.227-11, Patent Rights – Exceptional Circumstances, and HHSAR Clause 352.227-14, Rights in Data – Exceptional Circumstances, would apply to the solicitation and any resultant contracts.

Offerors will be required to have an active Assurance from the NIH’s Office of Laboratory Animal Welfare (OLAW) and a current AAALAC accreditation to be eligible for an IDIQ award. This requirement will be included in the solicitation for this requirement, if issued.

CONFIDENTIALITY

No proprietary, classified, confidential, or sensitive information should be included in your response.

The Government reserves the right to use any non-proprietary technical information in any resultant solicitation(s).